DISORDERS OF POTASSIUM HANDLING

Question 1

What is the average daily intake of potassium in the diet?

Answer 1

40-120 mmol

Question 2

What percentage of the filtered potassium does the kidney end up excreting?

Answer 2

5-15%

Question 3

Where in the nephron is most of the potassium that is to be excreted by the kidney secreted?

Answer 3

In the collecting duct

Question 4

What is the major driving force of potassium movement in and out of the basal membrane cell in the nephron?

Answer 4

Na/K ATPase

Question 5

What are the two main types of potassium channel found in the kidney?

Answer 5

ROMK - present throughout the nephron (apart from proximal tubule) but is the key secretory channel in the principal cells of the cortical collecting duct (same cells as the ENaC channels)

BK channels - also in collecting ducts. Generally closed but opened but high flow rates trigger a rise in intracellular calcium.

Question 6

Where in the nephron are most of the filtered potassium ions reabsorbed?

Answer 6

65% in the proximal tubule

30% in the thick ascending limb of the loop of Henle

Question 7

What is the transporter responsible for a lot of the potassium reabsorption from the thick ascending limb of the loop of Henle?

Answer 7

NKCC2 (Sodium, potassium and 2 chloride co-transporter)

Question 8

Which cells in the cortical collecting duct are responsible for the secretion of potassium?

Answer 8

Principal cells

Question 9

What are the two ways that potassium can leave the cell at the lumen side of the principal cell in the cortical collecting duct of the nephron?

Answer 9

ROMK channel

KCC (potassium chloride co-transporter)

Question 10

Which cells in the cortical collecting duct are responsible for reabsorption of potassium?

Answer 10

Type A intercalated cells

Question 11

What is the transporter responsible for the reabsorption of potassium in the type A intercalated cells of the cortical collecting ducts?

Answer 11

H/K ATPase

Question 12

How does flow rate through the collecting ducts affect potassium secretion?

Answer 12

Higher the flow rate the higher the amount of potassium that can be secreted and excreted.

Question 13

What drug decreases the potassium reabsorption by inhibiting the NKCC2 co-transporter in the thick ascending limb of the loop of Henle?

Answer 13

Furosemide

Question 14

What hormone increases potassium secretion by stimulating the Na/K ATPase in the principal cells of the cortical collecting duct?

Answer 14

Aldosterone

Question 15

What hormone increases potassium secretion by stimulating the introduction of more ROMK channels in the cortical collecting duct?

Answer 15

ADH

Question 16

What is the drug responsible for inhibiting potassium reabsorption in the type A intercalated cells of the cortical collecting duct?

Answer 16

Omeprazole

Question 17

Where in the kidney does furosemide have its affect on potassium movement in the kidney?

Answer 17

Thick ascending limb of the loop of Henle - inhibits NKCC2 (sodium, potassium and chloride co-transporter)

Question 18

Where in the kidney does aldosterone have its affect on potassium movement in the kidney?

Answer 18

Cortical collecting ducts - stimulates/promotes transcription of Na/K ATPase.

Question 19

Where in the kidney does ADH have its affect on potassium movement in the kidney?

Answer 19

Cortical collecting ducts - Promotes transcription of ROMK channels.
However, also reduces flow rate which will reduce potassium secretion.

Question 20

Where in the kidney does omeprazole have its affect on potassium movement in the kidney?

Answer 20

Cortical collecting ducts - Inhibits H/K ATPase

Question 21

What is the effect of beta-blockers on potassium levels in the plasma?

Answer 21

Beta-blockers inhibit the Na/K ATPase in a cell membrane, thereby increasing the amount of extracellular potassium.

Question 22

What is the effect of beta-agonists on potassium levels in the plasma?

Answer 22

Beta-agonists stimulate Na/K ATPase in the cell membrane, thereby reducing the amount of extracellular potassium

Question 23

How does pH affect potassium levels in the plasma?

Answer 23

H+ ions entering the cell can displace K ions, hence increasing the level of extracellular potassium. Acidosis can therefore induce hyperkalaemia.

Question 24

How do thyroid hormone affect potassium levels in the plasma?

Answer 24

Thyroid hormones promote Na/K ATPase synthesis and hence reduces the level of extracellular potassium.

Question 25

What drug decreases potassium secretion by inhibiting the ENaC (epithelial sodium channels) in the cortical collecting duct, thereby preventing the creation of the negative voltage required for potassium secretion through the ROMK channels?

Answer 25

Amiloride

Question 26

Where in the kidney does amiloride have its affect on potassium movement in the kidney?

Answer 26

Cortical collecting ducts - block ENaC thereby preventing the creation of the negative voltage required for potassium secretion through the ROMK channels.

Question 27

How does pH affect renal secretion of potassium?

Answer 27

Increase in H+ ions leads to stimulation the H/K ATPase in the cortical collecting duct and hence increase in K reabsorption.
Increase in pH also increases potassium channel and Na/K ATPase activity in the lumer side of the basal cells in the collecting duct.
As a result, potassium secretion is reduced in acute acidosis and increased in acute alkalosis

Question 28

How does sodium delivery to the collecting ducts affect potassium secretion?

Answer 28

If sodium levels fall then there is less substrate for the Na/K ATPase so less potassium is excreted. Also reduced sodium reabsorption means that the lumen is less negative and therefore passive potassium secretion through ROMK channels is reduced.

Question 29

How does magnesium affect potassium secretion?

Answer 29

Intracellular magnesium can bind and block ROMK channels and thereby reduced potassium secretion. Low magnesium can therefore predispose someone to hypokalaemia which is hard to treat until magnesium stores have been replenished.

Question 30

Where in the kidney do thiazides have their affect on potassium movement in the kidney?

Answer 30

Distal tubule - block NCC which blocks sodium reabsorption. Potassium reabsorption in the distal tubule is dependent on sodium reabsorption and therefore there is reduced potassium reabsorption.

Question 31

Where in the kidney does spiranolactone have its affect on potassium movement in the kidney?

Answer 31

Collecting ducts - antagonises the affects of aldosterone and therefore reduces potassium secretion.

Question 32

What are the causes of hypokalaemia?

Answer 32

Shift into cells:
Penicillins
Aminoglycosides
Insulin excess or overdose
Metabolic alkalosis
Salbutamol and other beta agonists - increase Na/K ATPase activity

Renal loss:
Vomiting
Hyperaldosteronism
Glycyrrhizinic acid in licorice upregulates mineralocorticoid receptors
Mutations in the NKCC2 transporter, the NCC transporter or the ENaC channel.
Renal tubular acidosis
Low magnesium
Diuretics - Loop, diuretics, thiazides, and osmotic diuretics

Gut loss:
Diarrhoea
Vomiting
Low potassium diet

Question 33

How does vomiting cause hypokalaemia?

Answer 33

Loss of gastric acid causes a metabolic alkalosis which results in renal loss of potassium.

Question 34

What are the clinical features of hypokalaemia?

Answer 34

Muscle weakness
Constipation
Gut ileus
Increases automaticity and delays repolarization of cardiac cells - predisposes to dysrhythmias such as ectopic beats, AV block, AF and VF.

Question 35

What are the ECG changes associated with hypokalaemia?

Answer 35

Progressive lengthening of the PR interval
ST depression
Flat T waves
Increase in U waves

Question 36

How is someone found to be hypokalaemic managed?

Answer 36

Oral potassium supplements
IV potassium chloride
Potassium sparing diuretic (spironolactone) can take place of other diuretic (furosemide)

Question 37

What are the causes of hyperkalaemia?

Answer 37

Shift out of cells:
Beta-blockers - decrease Na/K ATPase activity
Metabolic acidosis - H+ ions enter cell and shift K+ ions out of cell
Diabetes mellitus - insulin deficiency

Renal retention:
Renal failure
Potassium sparing diuretics - spironolactone
ACE inhibitors
Angiotensin blockers - losortan
Functional hypoaldosteronism - adrenal disease, hyporeninaemia (diabetic nephropathy)
NSAIDs

Question 38

What are the clinical features of hyperkalaemia?

Answer 38

Muscle weakness
Ventricular fibrillation causing cardiac arrest
Other dysrhythmias

Question 39

What are the ECG changes associated with hyperkalaemia?

Answer 39

Loss of P waves
Widening of QRS
Loss of ST segment
Tall-wide T waves
Peaked T waves

Question 40

How is someone found to be hyperkalaemic managed?

Answer 40

Calcium gluconate - buys time before cardiac event does not treat
Insulin (plus glucose to avoid hypoglycaemia) helps push K back into cells
Beta agonists - also help push K back into cells
Sodium bicarbonate produces a temporary alkalosis which also promotes K to go back into cells
Long term management through diuretics such as furosemide combined with hydration
Dialysis if renal function severely impaired.

Question 41

How does metabolic alkalosis cause hypokalaemia?

Answer 41

Alkalosis stimulates non renal Na/H exchanger on the surface of cells to push out H+. As a result, the Na/K ATPase must work harder to push the sodium back out. The net effect is a loss of potassium from the plasma.

Also the H/K exchanger pushes H+ out whilst bringing K in.